tbuckley/cabot-search huggingface dataset:
Mavacamten for Obstructive Hypertrophic Cardiomyopathy With or Without Hypertension
Authors: Andrew Wang, John A. Spertus, Daniel M. Wojdyla, Theodore P. Abraham, Ester Kim Nilles, Anjali Tiku Owens, Sara Saberi, Sharon Cresci, Amy Sehnert, Neal K. Lakdawala
Journal: JACC Heart Failure (2023)
Evolution and spread of Plasmodium falciparum mutations associated with resistance to sulfadoxine–pyrimethamine in central Africa: a cross-sectional study
Authors: Emilie Guémas, Romain Coppée, Sandie Ménard, Milena du Manoir, Sandrine Nsango, Dieudonné Makaba Mvumbi, Emmanuel Nakoune, Carole Else Eboumbou Moukoko, Marielle Karine Bouyou Akotet, Tatfeng Youtchou Mirabeau, Sylvie Manguin, Doudou Malekita Yobi, Jean Akiana, Lady Charlène Kouna, Denise Patricia Mawili Mboumba, Dominique Fatima Voumbo-Matoumona, Alliance-Laure Otam, Pierre-Alain Rubbo, Jean-Pierre Lombart, Elisabeth Kwanai, Olivia Cohen, Xavier Iriart, Lawrence Ayong, Jean Bernard Lekana-Douki, Frédéric Ariey, Antoine Berry
Journal: The Lancet Microbe (2023)

Efficacy of sulfadoxine-pyrimethamine, the malaria chemoprophylaxis used in pregnant women, and in children when combined with amodiaquine, is threatened by the accumulation of mutations in the Plasmodium falciparum dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes. Data on the prevalence of resistant alleles in central Africa and the new pfdhps I431V mutation, particularly associated with other mutations to form the pfdhps vagKgs allele, are scarce. We explored the frequency and geographical distribution of pfdhps and pfdhfr mutations in central Africa in 2014-18, and assessed the evolutionary origin of the vagKgs allele.
Metachronous colorectal cancer risk according to Lynch syndrome pathogenic variant after extensive versus partial colectomy in the Netherlands: a retrospective cohort study
Authors: Ellis L Eikenboom, Sarah Moen, Monique E van Leerdam, Grigorios Papageorgiou, Michail Doukas, Pieter J Tanis, Evelien Dekker, Anja Wagner, Manon C W Spaander
Journal: The Lancet. Gastroenterology & hepatology (2023)
Single basolateral amygdala neurons in macaques exhibit distinct connectional motifs with frontal cortex
Authors: Zachary R. Zeisler, Liza London, William G. Janssen, J. Megan Fredericks, Catherine Elorette, Atsushi Fujimoto, Huiqing Zhan, Brian E. Russ, Roger L. Clem, Patrick R. Hof, Frederic M. Stoll, Peter H. Rudebeck
Journal: Neuron (2023)
Fe(III)-Shikonin supramolecular nanomedicines as immunogenic cell death stimulants and multifunctional immunoadjuvants for tumor vaccination
Authors: Wenjie Feng, Wanrui Shi, Yanqi Cui, Jiajun Xu, Shuwei Liu, Hang Gao, Shoujun Zhu, Yi Liu, Hao Zhang
Journal: Theranostics (2023)

Immunoadjuvants, as an indispensable component of tumor vaccines, can observably enhance the magnitude, breadth, and durability of antitumor immunity. However, current immunoadjuvants suffer from different issues such as weak immunogenicity, inadequate cellular internalization, poor circulation time, and mono-functional bioactivity. Methods: Herein, we construct Fe3+-Shikonin metal-phenolic networks (FeShik) nanomedicines as immunogenic cell death (ICD) stimulants and multifunctional immunoadjuvants for tumor vaccination. The multifunctionality of FeShik nanomedicines is investigated by loading ovalbumin (OVA) as the model antigen to construct OVA@FeShik nanovaccines or 4T1 tumor cell fragment (TF) as homologous antigen to construct TF@FeShik nanovaccines. In vitro examinations including GSH responsive, •OH generation, colloid stability, cellular uptake, cytotoxicity mechanism of ferroptosis and necroptosis, ICD effect, the promotion of DC maturation and antigen cross-presentation were studied. In vivo observations including pharmacokinetics and biodistribution, antitumor effect, abscopal effect, immune memory effect, and biosafety were performed. Results: The presence of FeShik nanomedicines can significantly prolong the blood circulation time of antigens, increasing the bioavailability of antigens. Upon phagocytosis by tumor cells, FeShik nanomedicines can disassemble into Fe2+ and Shikonin in response to tumor microenvironments, leading to ICD of tumor cells via ferroptosis and necroptosis. Consequently, ICD-released autologous tumor cell lysates and pro-inflammatory cytokines not only stimulate DC maturation and antigen cross-presentation, but also promote macrophage repolarization and cytotoxic T lymphocyte infiltration, resulting in the activation of adaptive immune responses toward solid tumors. Conclusion: In a word, our FeShik supramolecular nanomedicines integrate bioactivities of ICD stimulants and immunoadjuvants, such as eradicating tumor cells, activating antitumor immune responses, modulating immunosuppressive tumor microenvironments, and biodegradation after immunotherapy. Encouraged by the diversity of polyphenols and metal ions, our research may provide a valuable paradigm to establish a large library for tumor vaccination.
Peptide-drug co-assembling: A potent armament against cancer
Authors: Can Wu, Manman Wang, Jinpan Sun, Yongyan Jia, Xiali Zhu, Gaizhi Liu, Yanhui Zhu, Yanbin Guan, Zhenqiang Zhang, Xin Pang
Journal: Theranostics (2023)

Cancer is still one of the major problems threatening human health and the therapeutical efficacies of available treatment choices are often rather low.Due to their favorable biocompatibility, simplicity of modification, and improved therapeutic efficacy, peptide-based self-assembled delivery systems have undergone significant evolution.Physical encapsulation and covalent conjugation are two common approaches to load drugs for peptide assembly-based delivery, which are always associated with drug leaks in the blood circulation system or changed pharmacological activities, respectively.To overcome these difficulties, a more elegant peptide-based assembly strategy is desired.Notably, peptide-mediated co-assembly with drug molecules provides a new method for constructing nanomaterials with improved versatility and structural stability.The co-assembly strategy can be used to design various nanostructures for cancer therapy, such as nanotubes, nanofibrils, hydrogels, and nanovesicles.Recently, these co-assembled nanostructures have gained tremendous attention for their unique superiorities in tumor therapy.This article describes the classification of assembled peptides, driving forces for co-assembly, and specifically, the design methodologies for various drug molecules in co-assembly.It also highlights recent research on peptide-mediated co-assembled delivery systems for cancer therapy.Finally, it summarizes the pros and cons of co-assembly in cancer therapy and offers some suggestions for conquering the challenges in this field.
1α,25(OH)<sub>2</sub>D<sub>3</sub> ameliorates insulin resistance by alleviating γδ T cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression
Authors: Peng Li, Ke Li, Wenhui Yuan, Yuqi Xu, Ping Li, Ruan Wu, Jingru Han, Zhinan Yin, Ligong Lu, Yunfei Gao
Journal: Theranostics (2023)

Background: Chronic inflammation caused by immune cells is the central link between obesity and insulin resistance. Targeting the inflammatory process is a highly promising method for reversing systemic insulin resistance. Methods: Blood samples were prospectively collected from 68 patients with type 2 diabetes. C57BL/6J mice were fed either a high-fat diet (HFD) or normal chow (NC). We performed phenotypical and functional analyses of immune cells using flow cytometry. Vitamin D receptor (VDR) knockout γδ T cells were constructed using Cas9-gRNA targeted approaches to identify 1α,25(OH)2D3/VDR signaling pathway-mediated transcriptional regulation of fructose-1,6-bisphosphatase (FBP1) in γδ T cells. Results: Serum vitamin D deficiency aggravates inflammation in circulating γδ T cells in type 2 diabetes patients. We defined a critical role for 1α,25(OH)2D3 in regulating glycolysis metabolism, protecting against inflammation, and alleviating insulin resistance. Mechanistically, 1α,25(OH)2D3-VDR promoted FBP1 expression to suppress glycolysis in γδ T cells, thereby inhibiting Akt/p38 MAPK phosphorylation and reducing inflammatory cytokine production. Notably, therapeutic administration of 1α,25(OH)2D3 restrained inflammation in γδ T cells and ameliorated systemic insulin resistance in obese mice. Conclusions: Collectively, these findings show that 1α,25(OH)2D3 plays an important role in maintaining γδ T cell homeostasis by orchestrating metabolic programs, and is a highly promising target for preventing obesity, inflammation, and insulin resistance.
Systemic delivery of glycosylated-PEG-masked oncolytic virus enhances targeting of antitumor immuno-virotherapy and modulates T and NK cell infiltration
Authors: Yuzhi Liang, Bing Wang, Qingjing Chen, Xingyue Fu, Chenwei Jiang, Zhiwen Lin, Qiuyu Zhuang, Yongyi Zeng, Xiaolong Liu, Da Zhang
Journal: Theranostics (2023)

Rationale: Immuno-virotherapy has emerged as a promising approach for cancer treatment, as it directly and cytotoxically eliminates tumors with systemic immune stimulation. However, the clinical efficacy of this approach remains limited by inappropriate delivery routes, robust antiviral responses, and the tumor immunosuppressive microenvironment. Methods: To address these challenges, we propose a surface engineering strategy that masks oncolytic herpes simplex virus (oHSV) with a galactose-polyethylene-glycol (PEG) polymer chain to minimize host antiviral responses and selectively targets tumors by limiting exposure to circulation upon systemic administration. We evaluated the antitumor efficacy of glycosylated-PEG-oHSV by examining tumor growth in animal models and analyzing tumor-infiltrating CD8+T cells and NK cells in the tumor microenvironment (TME). To assess the neutralizing antibody levels after systemic administration of glycosylated-PEG-oHSV, we utilized a mouse model and measured oHSV-specific IgG. Results: We demonstrate that the glycosylated-PEG modified oHSV does not affect the replication of oHSV yet exhibits high specificity to the asialoglycoprotein receptor (ASGPR) overexpressed in hepatocellular carcinoma cells. This results in selectively targeting cancer cells and deep penetration into tumors while avoiding spreading into the brain. Our approach also effectively reduces oHSV-specific neutralizing antibody levels to mitigate host antiviral immune response. Notably, our glycosylated-PEG-oHSV alleviates the immunosuppressive microenvironment within tumors by reducing regulatory T cells, augmenting the infiltration of activated CD8+T cells and NK cells with increasing release of anti-tumor cytokines, to impede tumor progression. Conclusion: Our findings offer a widely applicable and universal strategy to enhance cancer immuno-virotherapy through systemic administration of non-genetically engineered oncolytic viruses. This approach has the potential to overcome the limitations of current immune-virotherapy strategies and may improve clinical outcomes for cancer patients.
Theranostics with photodynamic therapy for personalized medicine: to see and to treat
Authors: Youchao Wang, Johannes Nikodemus Staudinger, Thomas L. Mindt, Gilles Gasser
Journal: Theranostics (2023)

Photodynamic Therapy (PDT) is an approved treatment modality, which is presently receiving great attention due to its limited invasiveness, high selectivity and limited susceptibility to drug resistance.Another related research area currently expanding rapidly is the development of novel theranostic agents based on the combination of PDT with different imaging technologies, which allows for both therapy and diagnosis.This combination can help to address issues of suboptimal biodistribution and selectivity through regional imaging, while therapeutic agents enable an effective and personalized therapy.In this review, we describe compounds, whose structures combine PDT photosensitizers with different imaging probes -including examples for near-infrared optical imaging, magnetic resonance imaging (MRI) and nuclear imaging (PET or SPECT), generating novel theranostic drug candidates.We have intentionally focused our attention on novel compounds, which have already been investigated preclinically in vivo in order to demonstrate the potential of such theranostic agents for clinical applications.
Piezo1 specific deletion in macrophage protects the progression of liver fibrosis in mice
Authors: Shangfei Luo, Xiaoduo Zhao, Jintao Jiang, Bo Deng, Silin Liu, Honglin Xu, Qiaorui Tan, Yu'an Chen, Ziyan Zhang, Xianmei Pan, Rentao Wan, Xiaoting Chen, Youfen Yao, Jing Li
Journal: Theranostics (2023)

Background and Aims: Liver fibrosis is the common pathological pathway of chronic liver diseases and its mechanisms of which have not been fully declared. Macrophages play essential roles in progression of liver fibrosis partially by sensing abnormal mechanical signals. The aim of the study is to investigate the functions of macrophage Piezo1, a mechano-sensitive ion channel, in liver fibrosis. Approach and Results: Immunofluorescence in human and murine fibrotic liver samples revealed that expression of macrophage Piezo1 was increased. Myeloid-specific Piezo1 knockout (Piezo1ΔLysM) attenuated liver fibrosis by decreased collagen deposition and epithelial-mesenchymal transition (EMT). In Piezo1ΔLysM mice, less inflammation during development of liver fibrosis was observed by lessened macrophage infiltration, decreased M1 polarization and expression of inflammatory cytokines. RNA-seq data showed macrophage Piezo1 regulated transcription of cathepsin S (CTSS). Piezo1ΔLysM inhibited expression and activity of CTSS in vitro and in vivo and regulated T cell activity. Furthermore, inhibition of CTSS reversed macrophage inflammatory response driven by Piezo1 activation and LPS. Macrophage Piezo1 activation promoted CTSS secretion due to increased activity of Ca2+-dependent calpain protease induced by Ca2+ influx to cleave lysosome-associated membrane protein-1 (LAMP1). Pharmacological inhibition of calpain activity partially blocked Piezo1 mediated CTSS secretion. Conclusions: Macrophage Piezo1 deficiency limits the progression of liver fibrosis by inhibited inflammatory response and decreased secretion of CTSS. These findings suggest that targeting Piezo1 channel may be a potential strategy for treating hepatic fibrosis.
Universal theranostic CRISPR/Cas13a RNA-editing system for glioma
Authors: Ye Wu, Yunfei Wang, Junhu Zhou, Jianhao Wang, Qi Zhan, Qixue Wang, Eryan Yang, Weili Jin, Fei Tong, Jixing Zhao, Biao Hong, Junrui Liu, Chunsheng Kang
Journal: Theranostics (2023)

Background:The CRISPR/Cas13a system offers the advantages of rapidity, precision, high sensitivity, and programmability as a molecular diagnostic tool for critical illnesses.One of the salient features of CRISPR/Cas13a-based bioassays is its ability to recognize and cleave the target RNA specifically.Simple and efficient approaches for RNA manipulation would enrich our knowledge of disease-linked gene expression patterns and provide insights into their involvement in the underlying pathomechanism.However, only a few studies reported the Cas13a-based reporter system for in vivo molecular diagnoses.Methods: A tiled crRNA pool targeting a particular RNA transcript was generated, and the optimally potential crRNA candidates were selected using bioinformatics modeling and in vitro biological validation methods.For in vivo imaging assessment of the anti-GBM effectiveness, we exploited a human GBM patient-derived xenograft model in nude mice. Results:The most efficient crRNA sequence with a substantial cleavage impact on the target RNA as well as a potent collateral cleavage effect, was selected.In the xenografted GBM rodent model, the Cas13a-based reporter system enabled us in vivo imaging of the tumor growth.Furthermore, systemic treatments using this approach slowed tumor progression and increased the overall survival time in mice.Conclusions: Our work demonstrated the clinical potential of a Cas13a-based in vivo imaging method for the targeted degradation of specific RNAs in glioma cells, and suggested the feasibility of a tailored approach like Cas13a for the modulation of diagnosis and treatment options in glioma.
Inhalation of acidic nanoparticles prevents doxorubicin cardiotoxicity through improvement of lysosomal function
Authors: Yohan Santin, Karina Formoso, Fraha Haidar, Maria Del Pilar Oreja Fuentes, Florence Bourgailh, Nesrine Hifdi, Karim Hnia, Yosra Doghri, Jessica Resta, Camille Champigny, Séverine Lechevallier, Maximin Détrait, Grégoire Cousin, Malik Bisserier, Angelo Parini, Frank Lezoualc'h, Marc Verelst, Jeanne Mialet-Perez
Journal: Theranostics (2023)

Doxorubicin (Dox) is an effective anticancer molecule, but its clinical efficacy is limited by strong cardiotoxic side effects. Lysosomal dysfunction has recently been proposed as a new mechanism of Dox-induced cardiomyopathy. However, to date, there is a paucity of therapeutic approaches capable of restoring lysosomal acidification and function in the heart. Methods: We designed novel poly(lactic-co-glycolic acid) (PLGA)-grafted silica nanoparticles (NPs) and investigated their therapeutic potential in the primary prevention of Dox cardiotoxicity in cardiomyocytes and mice. Results: We showed that NPs-PLGA internalized rapidly in cardiomyocytes and accumulated inside the lysosomes. Mechanistically, NPs-PLGA restored lysosomal acidification in the presence of doxorubicin or bafilomycin A1, thereby improving lysosomal function and autophagic flux. Importantly, NPs-PLGA mitigated Dox-related mitochondrial dysfunction and oxidative stress, two main mechanisms of cardiotoxicity. In vivo, inhalation of NPs-PLGA led to effective and rapid targeting of the myocardium, which prevented Dox-induced adverse remodeling and cardiac dysfunction in mice. Conclusion: Our findings demonstrate a pivotal role for lysosomal dysfunction in Dox-induced cardiomyopathy and highlight for the first time that pulmonary-driven NPs-PLGA administration is a promising strategy against anthracycline cardiotoxicity.
Engineering CAR-T cells for radiohapten capture in imaging and radioimmunotherapy applications
Authors: Keifer Kurtz, Laura Eibler, Megan M. Dacek, Lukas M. Carter, Darren R. Veach, Samantha Lovibond, Emma Reynaud, Sarah Qureshy, Michael R. McDevitt, Christopher Bourne, Sebastien Monette, Blesida Punzalan, Shireen Khayat, Svena Verma, Adam L. Kesner, Nai-Kong V. Cheung, Heiko Schöder, Leah Gajecki, Sarah M. Cheal, Steven M. Larson, David A. Scheinberg, Simone Krebs
Journal: Theranostics (2023)

The
Photocurable injectable Janus hydrogel with minimally invasive delivery for all-in-one treatment of gastric perforations and postoperative adhesions
Authors: Xiaoqi Wu, Zihan Wang, Jie Xu, Liu Yu, Maoyu Qin, Jianfeng Li, Sitian Liu, Weihan Zheng, Zeyu Li, Jun Ouyang, Yanbing Li, Guoxin Li, Ling Wang, Wenhua Huang, Yaobin Wu
Journal: Theranostics (2023)

Background: Surgical sutures for sealing gastric perforations (GP) are associated with severe inflammation and postoperative adhesions. Hydrogel bioadhesives offer a potential alternative for sutureless repair of GP; however, their application in minimally invasive surgery is limited due to their prefabricated patch-form, lacking in situ gelation capability. In this study, we emphasized an all-in-one minimally invasive strategy for sutureless repair of acute GP. Methods: an injectable photocurable Janus hydrogel was synthesized, and their ability to seal GP was performed. A rat GP model was used to verify the wound healing and antiadhesion efficiency of hydrogels, and a rabbit GP model was used to verify their laparoscopic feasibility. A fresh human corpse GP model was further employed to verify the user-friendliness of a minimally invasive deliverable (MID) device. A minipig GP model was utilized to evaluate the all-in-one minimally invasive strategy for the treatment of acute GP. Results: Such injectable Janus hydrogel exhibited asymmetric adhesiveness, where the inner-facing side of the hydrogel displays strong sealing and wound healing abilities for GP, while the outward-facing side prevents postoperative adhesion formation. We further developed a minimally invasive deliverable (MID) device integrating hydrogel-delivery parts and photocrosslinking-gelation parts in a laparoscope system. The precise delivery and rapid fluid-tight sealing process of the injectable Janus hydrogel using the MID device for in situ GP repair were demonstrated in a simulated clinical scenario. The in vivo effectiveness of GP sutureless repair was successfully validated in porcine models, with further exploration of the underlying mechanism. Conclusions: Our findings reveal that the injectable Janus hydrogel offers an all-in-one strategy for sutureless GP repair and concurrent prevention of postoperative adhesion formation by incorporating the MID device in minimally invasive surgery, presenting the significant potential to reduce patient surgical complications.
Table of Contents
Authors: Kyung Lee, John Cijiang He, T Alp Ikizler, Clarkson Crane, Pranav Garimella, Georg Heinze, Kai-Uwe Eckardt, Cynthia Delgado, Hiddo Heerspink, Roberto Pecoits-Filho, Ana Ricardo, Bénédicte Stengel, Marcello Tonelli, Michael Cheung, Michel Jadoul, Wolfgang Winkelmayer, Holly Kramer, Tyrone Harrison, Lauren Albrecht, Renata Pereira, Isidro Salusky, Molly Fisher, Melissa Fazzari, Uriel Felsen, David Hanna, Nataliya Tappan, Christina Wyatt, Matthew Abramowitz, Michael Ross, Evert Cleenders, Priyanka Koshy, Elisabet Van Loon, Katrien Lagrou, Kurt Beuselinck, Graciela Andrei, Marta Crespo, Katrien De Vusser, Dirk Kuypers, Evelyne Lerut, Kris Mertens, Olga Mineeva-Sangwo, Parmjeet Randhawa, Aleksandar Senev, Robert Snoeck, Ben Sprangers, Claire Tinel, Amaryllis Craenenbroeck, Jan Van Den Brand, Marc Van Ranst, Geert Verbeke, Maarten Coemans, Maarten Naesens, Tamas Szili-Torok, Uwe Tietge, Max Verbeek, Stephan Bakker, Martin De Borst, Agathe Truchot, Marc Raynaud, Alexandre Loupy
Journal: Kidney International (2023)
Corrigendum to “Successful kidney-alone transplantation in a patient with PH1 on combination RNA-interference therapy.” Kidney International, 2023;104:203–204
Authors: Elisabeth L. Metry, Lisa J. Deesker, Sander F. Garrelfs, Michiel J.S. Oosterveld, Kerensa M. Beekman, Elisabeth A.M. Cornelissen, Linda Koster-Kamphuis, Jaap W. Groothoff
Journal: Kidney International (2023)